Age‐ and endometrial microbiota‐related delay in development of endometrial receptivity

PURPOSE: We evaluated factors affecting the development of endometrial receptivity according to age and changes in the endometrial microbiota. METHODS: We recruited patients with infertility who underwent transcriptomic analyses of endometrial receptivity and the endometrial microbiome prior to frozen embryo transfer. An endometrial biopsy was performed 108 h after initial progesterone administration. RESULTS: In 185 tests from 185 eligible patients, the results of endometrial receptivity analysis were receptive in 111 (60.0%) patients and pre‐receptive in 74 (40.0%) patients. Compared with receptive patients, pre‐receptive patients had significantly older ages (36.0 ± 0.5 vs. 38.2 ± 0.5, p = 0.0021), a smaller proportion of normal Lactobacillus‐dominant microbiota (27.9% vs. 12.2%), and a greater proportion of microbiota with ultralow biomass (22.5% vs. 41.9%) (p = 0.0074). Patient age (adjusted odds ratio: 1.08, 95% confidence interval: 1.01–1.16, p = 0.0351) and a microbiome with ultralow biomass (adjusted odds ratio: 3.82, 95% confidence interval: 1.49–9.82, p = 0.0039) were independent predictive factors for pre‐receptive endometrium. CONCLUSIONS: Older age was accompanied by a decrease in Lactobacillus‐dominant microbiota; aging and endometrial microbiota with ultralow biomass were significantly associated with pre‐receptive endometrium. Our findings suggest that the quantity (rather than proportion) of Lactobacillus in the endometrium is important in the development of endometrial receptivity.